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A Randomized, Double-blind, Placebo-Controlled Trial

Edwin K. Kuffner, MD; Richard C. Dart, MD, PhD; Gregory M. Bogdan, PhD; Robert E. Hill, BSMJ; Edmund Casper, MD; Lisa Darton, MD

Arch Intern Med. 2001;161:2247-2252.

Background  Retrospective reports suggest that therapeutic doses of acetaminophen may be associated with fulminant hepatic failure and death in alcoholic patients. Millions of patients use acetaminophen; the prevalence of alcoholism in the United States is 5% to 10%.

Objective  To determine if hepatic injury was associated with maximal therapeutic dosing of acetaminophen to chronic alcohol abuse patients immediately following cessation of alcohol intake (the presumed time of maximal vulnerability).

Methods  Patients entering an alcohol detoxification center were enrolled in a randomized, double-blind, placebo-controlled trial. Exclusion criteria were baseline values of aspartate or alanine aminotransferase greater than 120 U/L, international normalized ratio greater than 1.5, serum acetaminophen level greater than 20 mg/L, or a history of ingesting more than 4 g/d of acetaminophen. Acetaminophen, 1000 mg, or placebo was administered orally 4 times daily for 2 consecutive days and liver test results were monitored for 2 more days. Acetaminophen was not administered until the alcohol had been eliminated.

Results  There were 102 patients in the acetaminophen-treated group and 99 patients in the placebo-treated (control) group. Demographic data, alcohol history, and baseline blood test results were similar in both groups. The mean (SD) aspartate aminotransferase level on day 4 was 38.0 ± 26.7 U/L in the acetaminophen-treated group and 37.5 ± 27.6 U/L in the placebo-treated group. There were 4 patients in the acetaminophen-treated group and 5 in the placebo-treated group who developed an increase in their serum aspartate aminotransferase level to greater than 120 U/L; it did not exceed 200 U/L in any patient. The mean (SD) international normalized ratio on day 4 was 0.96 ± 0.09 in the acetaminophen-treated group and 0.98 ± 0.11 in the placebo-treated group.

Conclusion  Repeated administration of the maximum recommended daily doses of acetaminophen to long-term alcoholic patients was not associated with evidence of liver injury.

From the Rocky Mountain Poison and Drug Center, Denver Health Authority (Drs Kuffner, Dart, and Bogdan and Mr Hill); Department of Psychiatry, Denver Health Medical Center, Denver Health Authority (Drs Casper and Darton); and Department of Surgery, University of Colorado Health Sciences Center (Drs Kuffner and Dart and Mr Hill), Denver.

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